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  • Title: Polymorphisms in CYP19A1 and NFKB1 genes are associated with cutaneous melanoma risk in southern Brazilian patients.
    Author: Escobar GF, Arraes JA, Bakos L, Ashton-Prolla P, Giugliani R, Callegari-Jacques SM, Santos S, Bakos RM.
    Journal: Melanoma Res; 2016 Aug; 26(4):348-53. PubMed ID: 27145040.
    Abstract:
    BACKGROUND: Melanoma is the leading cause of death from skin cancers and its etiology is complex. Recent discoveries related to genetic risk factors are helping us to understand melanoma pathogenesis better. Nuclear factor-κB (NF-κB) has a critical role in immunity, inflammation, and tumor growth. The 94ins/del ATTG (rs28362491) polymorphism located in the NFKB1 gene has been associated to various cancers and the ATTG2/ATTG2 genotype was correlated to melanoma risk in Sweden. The CYP19A1 gene encodes the enzyme aromatase, which is active in malignant melanoma tissue. In addition, the CYP19A1 TCT insertion/deletion variant in intron 4 (rs11575899) has been associated with an increased incidence of cancer, albeit with conflicting results. The goal of this study was to investigate possible associations between these two gene variants and melanoma. METHODS: In this case-control study, we evaluated 117 cutaneous melanoma patients and 116 controls from southern Brazil. Genotyping of rs28362491 and rs11575899 was carried out by means of PCR amplification and capillary electrophoresis. Logistic regression was used to obtain odds ratios (ORs) of melanoma, according to genotypes. RESULTS: We identified an association between the ATTG2/ATTG2 and melanoma [OR=1.78; 95% confidence interval (CI): 1.06-3.00; P=0.03]. In addition, there was a dose effect: for each ins allele in the genotype, the risk for melanoma increased (OR=1.51; 95% CI: 1.08-2.11; P=0.017). As regards the CYP19A1 variant, genotype 11 (del/del) was more frequent in patients than in controls (OR=1.85; 95% CI 1.06-3.22; P=0.03). CONCLUSION: The NFKB1 ATTG2/ATTG2 and CYP19A1 del/del genotypes are significantly associated with melanoma and could be genetic markers of melanoma susceptibility in southern Brazilian population.
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